Abstract 1547: Expression of epithelial-to-mesenchymal transition markers (EMT) in treated pancreatic duct adenocarcinoma

Abstract

Abstract Background: Pancreatic duct adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis. Epithelial to mesenchymal transition (EMT) plays an important role in the progression, metastasis and chemoresistance of PDAC. However the expression of EMT markers and their clinical significance in PDAC patients who received neoadjuvant therapy are not clear. Methods: One hundred and twenty cases were included in this study. All patients received neoadjuvant chemoradiation therapy and underwent surgical resection at our institution from 1999 to 2007. Expressions of EMT markers, including Zeb-1, E-cadherin, vimentin and N-cadherin, were evaluated by immunohistochemistry using tissue microarrays. The staining for Zeb-1 was categorized as positive (≥10% nuclear staining in tumor cells) and negative (<10% nuclear staining in tumor cells); the staining for E-cadherin was categorized as low (negative or <50% membranous staining) or high (≥50% membranous staining); the staining for vimentin and N-cadherin was categorized negative (<10% cytoplasmic staining) or positive (≥10% cytoplasmic staining). The expression results were correlated with clinicopathologic parameters and survival. All the statistical analyses were carried out with the SPSS software. Results: Among 120 cases, 45 (37.5%) were positive for Zeb-1, 25 (20.8 %) were E-cadherin-low, 14 (11.7%) were positive for vimentin, and 2 (1.7%) were positive for N-cadherin. There was negative correlation between the expression of E-cadherin and vimentin (p=0.03). E-cadherin-low and positive vimentin expression correlated with poor differentiation (p=0.02 and p=0.004, respectively). However, no correlations between the EMT markers with other clinical pathologic parameters were found (p>0.05). The median overall survival (OS) and disease-free survival (DFS) were 35.3 ± 2.8 months and 15.9 ± 3.6 months, respectively, in vimentin-negative group compared to 16.1 ± 1.1 months (p=0.03) and 7.0 ± 1.1 months (p=0.02), respectively, in vimentin-positive group. There were no correlation between the expression of Zeb-1, E-cadherin or N-cadherin and survival (P>0.05). In multivariate analysis, expression of vimentin was an independent predictor of shorter OS [HR (95% CI): 2.57 (1.34-4.93), p=0.004] and DFS [HR (95% CI): 2.80 (1.45-5.43), p=0.002]. Conclusion: Our results show that EMT markers are frequently expressed in treated PDAC. Expression of vimentin is a prognostic biomarker for both OS and DFS in patients with PDAC who received neoadjuvent therapy and surgery. Citation Format: Minhua Wang, Jeannelyn S. Estrella, Matthew H. Katz, Asif Rashid, Jeffrey E. Lee, Anirban Maitra, Robert A. Wolff, Gauri R. Varadhachary, Huamin Wang. Expression of epithelial-to-mesenchymal transition markers (EMT) in treated pancreatic duct adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1547.